Schultz et al. (1998) Proc. Natl. Acad. Sci. USA 95, 5857-5864
Letunic et al. (2012) Nucleic Acids Res , doi:10.1093/nar/gkr931

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DDHD

SMART accession number:	SM01127
Description:	The DDHD domain is 180 residues long and contains four conserved residues that may form a metal binding site. The domain is named after these four residues. This pattern of conservation of metal binding residues is often seen in phosphoesterase domains. This domain is found in retinal degeneration B proteins, as well as a family of probable phospholipases. It has been shown that this domain is found in a longer C terminal region that binds to PYK2 tyrosine kinase. These proteins have been called N-terminal domain-interacting receptor (Nir1, Nir2 and Nir3) ((PUBMED:10022914)). This suggests that this region is involved in functionally important interactions in other members of this family.
Family alignment:	View or CHROMA formatCLUSTALW formatMSF formatFASTA formatPIR format

There are 444 DDHD domains in 444 proteins in SMART's nrdb database.

Click on the following links for more information.

• Evolution (species in which this domain is found)

• Click on to expand nodes. To display all proteins with a DDHD domain in a specific node, click on it.

  This tree shows only several representative species. The complete taxonomic breakdown of all proteins with DDHD domain is also avaliable.

  Useful shortcuts: Expand all nodes or Collapse tree
  Go to specific node: Anopheles gambiae, Arabidopsis thaliana, Caenorhabditis elegans, Drosophila melanogaster, Homo sapiens, Mus musculus, Rattus norvegicus, Saccharomyces cerevisiae, Takifugu rubripes

• Cellular role (predicted cellular role)

• Cellular role: metabolism
  

• Literature (relevant references for this domain)

• Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.

  • Lev S, Hernandez J, Martinez R, Chen A, Plowman G, Schlessinger J
  • Identification of a novel family of targets of PYK2 related to Drosophila retinaldegeneration B (rdgB) protein.
  • Mol Cell Biol. 1999; 19: 2278-88
  • Display abstract

  • The protein tyrosine kinase PYK2 has been implicated in signaling pathwaysactivated by G-protein-coupled receptors, intracellular calcium, and stresssignals. Here we describe the molecular cloning and characterization of a novelfamily of PYK2-binding proteins designated Nirs (PYK2 N-terminaldomain-interacting receptors). The three Nir proteins (Nir1, Nir2, and Nir3) bindto the amino-terminal domain of PYK2 via a conserved sequence motif located inthe carboxy terminus. The primary structures of Nirs reveal six putativetransmembrane domains, a region homologous to phosphatidylinositol (PI) transfer protein, and an acidic domain. The Nir proteins are the human homologues of theDrosophila retinal degeneration B protein (rdgB), a protein implicated in thevisual transduction pathway in flies. We demonstrate that Nirs arecalcium-binding proteins that exhibit PI transfer activity in vivo. Activation ofPYK2 by agents that elevate intracellular calcium or by phorbol ester inducetyrosine phosphorylation of Nirs. Moreover, PYK2 and Nirs exhibit similarexpression patterns in several regions of the brain and retina. In addition,PYK2-Nir complexes are detected in lysates prepared from cultured cells or frombrain tissues. Finally, the Nir1-encoding gene is located at human chromosome17p13.1, in proximity to a locus responsible for several human retinal diseases. We propose that the Nir and rdgB proteins represent a new family ofevolutionarily conserved PYK2-binding proteins that play a role in the control ofcalcium and phosphoinositide metabolism downstream of G-protein-coupledreceptors.

• Links (links to other resources describing this domain)

• PFAM	DDHD

Send comments to Ivica Letunic